Enrichment in selected genotypes, basal core and precore mutations of hepatitis B virus in patients with hepatocellular carcinoma in Cameroon

Abstract

Worldwide, the development of hepatocellular carcinoma (HCC) is known to be influenced by several hepatitis B viral factors. However, the effect of hepatitis B virus (HBV) genotypes and a landscape of nucleotide changes affecting the precore (PC) and basal core promoter (BCP) during infection leading to HCC remain largely unknown in the Central Africa region. Thus, we performed a case‐control study on patients with HBV‐related HCC and matched controls without HCC but with chronic HBV infection. Genotypes and mutation spectrums were evaluated using a hemi‐nested amplification and sequencing analysis focused on the BCP and PC regions. We identified the co‐circulation of HBV quasi‐subgenotype A3 (QS‐A3) and genotype E in both groups. Interestingly, HBV‐QS‐A3 was significantly more prevalent in patients with HCC (80.0%) than in controls (31.9%, P = 4.5 E‐7, OR = 11.5, 95% CI: 3.8‐38.5). HBV mutation spectra and nucleotide changes were significantly more polymorphic in patients with HCC. Remarkably, HCC patients infected with HBV‐QS‐A3 were significantly more mutated compared to patients infected with genotype E (P < 0.0001). In addition, G:C>T:A transversions, generally associated with aflatoxin B1 exposure in tropical regions, were significantly more prevalent in HCC patients infected either with HBV‐QS‐A3 or HBV genotype E (P = 2.2 E‐05) when compared to controls. In conclusion, our results indicate that patients infected with HBV‐QS‐A3 are at increased risk to develop HCC. In addition, viral genomes isolated for patients with tumour are more heavily altered than those found in controls. Preferential targeting of these patients for antiviral treatment is of paramount importance to reduce future HCC incidence in Cameroon.

The genetic polymorphism down‐regulating HLA‐DRB1 enhancer activity facilitates HBV persistence, evolution and hepatocarcinogenesis in the Chinese Han population

“…With the progression of chronic HBV infection, especially during HBeAg seroconversion, viral mutations gradually occur. Some HBV mutations, especially those in the enhancer II/basal core promoter/precore (EnhII/BCP/PC) and the preS regions of the HBV genome, increase the risk of HCC and promote the malignant phenotypes of HCC cells after transfection 7‐9 . The HCC‐risk HBV mutations increase in their frequencies with the progression of chronic infection 10 .…”

Contemporary and historical human migration patterns shape hepatitis B virus diversity

“…2015a , 2017 ; Hou 2019 ). These associations between genotype-specific mutations in circulating African strains and clinical severity have been demonstrated, for instance with particular medically important mutations being mostly detected in the core gene of HBV strains isolated from patients with end stage liver diseases such as hepatocellular carcinoma (HCC) ( Amougou et al. 2019 ; Mak and Kramvis 2020 ; Mbamalu et al.…”

Autophagy plays a double-edged sword role in liver diseases

“…Chronic HBV or HCV infection may cause serious liver diseases, such as hepatocellular cancer, and cirrhosis [ 2 , 35 ]. HBV replication is regulated via multiple intracellular or extracellular factors, including specific hormones, inflammatory factors, and intracellular specific pathways [ 27 , 49 , 63 ].…”